The ANS may be separated into a central and a peripheral part. The central autonomic network (CAN) is located mainly in the forebrain and brain stem (Table 1.1). These areas form a complex reciprocally interconnected network. Converging information is received from somatosensory and visceral input. This input is processed under the influence of behavioral state, sleep-wake cycle, mood, etc. Based on this processing, autonomic (sympathetic and parasympathetic neurons), motor (e.g., respiratory function via phrenic neurons), and endocrine (e.g., pituitary gland) outflow is generated. The hypothalamus is the highest level of autonomic integration, under the influence of cortical and limbic structures (Fig. 1.3). It maintains homeostasis and adapts and integrates individual needs such as hunger, thirst, sexual function, and sleep. The peripheral autonomic nervous system (pANS) is composed of the sympathetic and parasympathetic branch (Fig. 1.1). The enteric nervous system (ENS) is the most independent part of the ANS. It is located in the submucosal plexus of Meissner and the myenteric plexus of Auerbach. It controls gastrointestinal function (peristalsis and secretion) from the pharyngoesophageal junction to the anal sphincter. Input comes from the brain stem via sympathetic and parasympathetic neurons and from approximately 30% sensory neurons within the gut.

As CAN is described in detail in many exquisite textbooks on the ANS (e.g., Low et al.), we will only present a very short overview following E.E. Benarroch’s description [5] to allow a basic understanding of the ANS necessary for clinical reasoning. Subsequently a special introduction to the gastrointestinal nervous system, to cardiocirculatory regulation, to control of sweating, and to sleep physiology will be given.

CAN includes the insular cortex, anterior cingulate cortex, amygdala, several nuclei of the hypothalamus, periaqueductal gray of the midbrain, parabrachial nucleus in the dorsolateral pons, and several medullary regions (nucleus of the solitary tract, ventrolateral reticular formation, raphe nuclei, dorsal vagal nucleus, nucleus ambiguus). CAN is hierarchically organized at all levels. The spinal level is the most caudal and constitutes the sympathetic segmental reflexes which are stimulus and target specific and the preganglionic parasympathetic neurons in the sacral spinal cord. More rostrally at the lower brain stem level, circulation, respiration, and micturition are controlled. At the upper brain stem level, autonomic control is integrated with pain and behavioral state. At the hypothalamic level, homeostasis is regulated. Forebrain structures control stress response and affective behavior, and the anterior limbic circuit integrates responses to emotions and behavior. In Table 1.1, the different structures of CAN and their functions are listed, as far as they are known. However, despite the hierarchical structure of CAN, its network architecture always has to be considered, particularly when interpreting cerebral images and lesions.

Inputs to CAN comprise visceral afferent inputs (visceroceptive information) and inputs from nociceptors, thermoreceptors, and muscle receptors. These signals are integrated at the different hierarchical levels of CAN. Dorsal horn neurons in lamina I represent the first line of integration and convey the information to higher regulatory centers (nucleus of the solitary tract, medullary network, thalamus, and insular cortex) (Fig. 1.5). There exists a viscerotopic representation in the insular cortex (viscerotopic homunculus). Other inputs to CAN originate from limbic and paralimbic areas and convey emotional information. Important humoral inputs are blood temperature, glucose level, osmolarity, and steroid hormones. Chemoreceptors in the ventral medulla react on changes in pCO₂ and pH and are involved in the control of respiratory and cardiovascular activity. O₂ level is controlled via receptors in carotid and aortic bodies.

Output is mediated by autonomic neurons, endocrine cells, and motor neurons (respiration, shivering, adaptive behavior). Autonomic outflow is mediated by preganglionic sympathetic and parasympathetic neurons. The sympathetic preganglionic neurons are located in the intermediolateral nucleus of T1–L3 levels of the spinal cord and are organized in functional units, each responsible for specific organ tasks. Preganglionic cholinergic neurons project via thin myelinated fibers to prevertebral and paravertebral ganglia. Postganglionic neurons use norepinephrine as transmitter except for cholinergic neurons innervating sweat glands. The parasympathetic output arises from preganglionic neurons within the brain stem and the sacral spinal cord. Most of the parasympathetic outflow is provided by the vagus nerve (dorsal nucleus and the ventrolateral portions of nucleus ambiguus) controlling the heart and respiratory and gastrointestinal function, the latter via the enteric nervous system except for the descending colon and rectum. The sacral preganglionic neurons are located in segments S2–S4 and are involved in the regulation of micturition, defecation, and sexual function. The so-called nucleus of Onuf at sacral levels S2–S3 innervates the external sphincters. All parasympathetic transmission is cholinergic and the preganglionic neurons synapse close to their target tissue.

The sympathetic neurotransmitter to the effector structures is norepinephrine, which acts via several subtypes of adrenergic receptors. Only sweat glands are innervated by acetylcholine (ACh). The primary neurotransmitter of the parasympathetic system is ACh. However, other mediators such as neuropeptides, NO, and ATP play an important role in the complex autonomic regulation.